Fine-tuning Mybl2 is required for proper mesenchymal-to-epithelial transition during somatic reprogramming

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Fine-tuning Mybl2 is required for proper mesenchymal-to-epithelial transition during somatic reprogramming. / Ward, Carl; Volpe, Giacomo; Cauchy, Pierre; Ptasinska, Anetta; Al Maghrabi, Ruba; Blakemore, Daniel; Nafria, Monica; Kestner, Doris; Frampton, Jonathan; Murphy, George; Buganim, Yosef; Kaji, Keisuke; Garcia, Paloma.

In: Cell Reports, Vol. 24, No. 6, 07.08.2018, p. 1496-1511.

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Ward, Carl ; Volpe, Giacomo ; Cauchy, Pierre ; Ptasinska, Anetta ; Al Maghrabi, Ruba ; Blakemore, Daniel ; Nafria, Monica ; Kestner, Doris ; Frampton, Jonathan ; Murphy, George ; Buganim, Yosef ; Kaji, Keisuke ; Garcia, Paloma. / Fine-tuning Mybl2 is required for proper mesenchymal-to-epithelial transition during somatic reprogramming. In: Cell Reports. 2018 ; Vol. 24, No. 6. pp. 1496-1511.

Bibtex

@article{6a0446426e7740208188d812e1dbb083,
title = "Fine-tuning Mybl2 is required for proper mesenchymal-to-epithelial transition during somatic reprogramming",
abstract = "During somatic reprogramming, Yamanaka{\textquoteright}s pioneer factors regulate a complex sequence of molecular events leading to the activation of a network of pluripotency factors, ultimately resulting in the acquisition and maintenance of a pluripotent state. Here we show that, contrary to the pluripotency factors studied so far, overexpression of Mybl2, inhibits somatic reprogramming. Our results demonstrate that Mybl2 levels are crucial for the dynamics of the reprogramming process. Mybl2 overexpression changes chromatin conformation, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for early immediate response genes known to be reprogramming blockers. These changes in chromatin landscape ultimately lead to a de-regulation of key genes important for the mesenchymal-to-epithelial transition. This work defines Mybl2 level as a gatekeeper for the initiation of reprogramming, providing further insights into the tight regulation and required coordination of molecular events necessary for changes in cell fate identity during the reprogramming process.",
keywords = "Stem cell, Induced Pluripotent Stem Cells, somatic reprogramming, mesenchymal to epithelial transition, chromatin landscape",
author = "Carl Ward and Giacomo Volpe and Pierre Cauchy and Anetta Ptasinska and {Al Maghrabi}, Ruba and Daniel Blakemore and Monica Nafria and Doris Kestner and Jonathan Frampton and George Murphy and Yosef Buganim and Keisuke Kaji and Paloma Garcia",
year = "2018",
month = aug,
day = "7",
doi = "10.1016/j.celrep.2018.07.026",
language = "English",
volume = "24",
pages = "1496--1511",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - Fine-tuning Mybl2 is required for proper mesenchymal-to-epithelial transition during somatic reprogramming

AU - Ward, Carl

AU - Volpe, Giacomo

AU - Cauchy, Pierre

AU - Ptasinska, Anetta

AU - Al Maghrabi, Ruba

AU - Blakemore, Daniel

AU - Nafria, Monica

AU - Kestner, Doris

AU - Frampton, Jonathan

AU - Murphy, George

AU - Buganim, Yosef

AU - Kaji, Keisuke

AU - Garcia, Paloma

PY - 2018/8/7

Y1 - 2018/8/7

N2 - During somatic reprogramming, Yamanaka’s pioneer factors regulate a complex sequence of molecular events leading to the activation of a network of pluripotency factors, ultimately resulting in the acquisition and maintenance of a pluripotent state. Here we show that, contrary to the pluripotency factors studied so far, overexpression of Mybl2, inhibits somatic reprogramming. Our results demonstrate that Mybl2 levels are crucial for the dynamics of the reprogramming process. Mybl2 overexpression changes chromatin conformation, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for early immediate response genes known to be reprogramming blockers. These changes in chromatin landscape ultimately lead to a de-regulation of key genes important for the mesenchymal-to-epithelial transition. This work defines Mybl2 level as a gatekeeper for the initiation of reprogramming, providing further insights into the tight regulation and required coordination of molecular events necessary for changes in cell fate identity during the reprogramming process.

AB - During somatic reprogramming, Yamanaka’s pioneer factors regulate a complex sequence of molecular events leading to the activation of a network of pluripotency factors, ultimately resulting in the acquisition and maintenance of a pluripotent state. Here we show that, contrary to the pluripotency factors studied so far, overexpression of Mybl2, inhibits somatic reprogramming. Our results demonstrate that Mybl2 levels are crucial for the dynamics of the reprogramming process. Mybl2 overexpression changes chromatin conformation, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for early immediate response genes known to be reprogramming blockers. These changes in chromatin landscape ultimately lead to a de-regulation of key genes important for the mesenchymal-to-epithelial transition. This work defines Mybl2 level as a gatekeeper for the initiation of reprogramming, providing further insights into the tight regulation and required coordination of molecular events necessary for changes in cell fate identity during the reprogramming process.

KW - Stem cell

KW - Induced Pluripotent Stem Cells

KW - somatic reprogramming

KW - mesenchymal to epithelial transition

KW - chromatin landscape

U2 - 10.1016/j.celrep.2018.07.026

DO - 10.1016/j.celrep.2018.07.026

M3 - Article

C2 - 30089261

VL - 24

SP - 1496

EP - 1511

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -